Taivassalo Tanja, Hepple Russell T
Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, United States.
Department of Physical Therapy, University of Florida, Gainesville, FL, United States.
Front Physiol. 2022 Jun 3;13:861617. doi: 10.3389/fphys.2022.861617. eCollection 2022.
The normal decline in skeletal muscle mass that occurs with aging is exacerbated in patients with chronic obstructive pulmonary disease (COPD) and contributes to poor health outcomes, including a greater risk of death. There has been controversy about the causes of this exacerbated muscle atrophy, with considerable debate about the degree to which it reflects the very sedentary nature of COPD patients vs. being precipitated by various aspects of the COPD pathophysiology and its most frequent proximate cause, long-term smoking. Consistent with the latter view, recent evidence suggests that exacerbated aging muscle loss with COPD is likely initiated by decades of smoking-induced stress on the neuromuscular junction that predisposes patients to premature failure of muscle reinnervation capacity, accompanied by various alterations in mitochondrial function. Superimposed upon this are various aspects of COPD pathophysiology, such as hypercapnia, hypoxia, and inflammation, that can also contribute to muscle atrophy. This review will summarize the available knowledge concerning the mechanisms contributing to exacerbated aging muscle affect in COPD, consider the potential role of comorbidities using the specific example of chronic kidney disease, and identify emerging molecular mechanisms of muscle impairment, including mitochondrial permeability transition as a mechanism of muscle atrophy, and chronic activation of the aryl hydrocarbon receptor in driving COPD muscle pathophysiology.
随着年龄增长而出现的骨骼肌质量正常下降，在慢性阻塞性肺疾病（COPD）患者中会加剧，并导致不良健康后果，包括更高的死亡风险。关于这种加剧的肌肉萎缩的原因一直存在争议，对于它在多大程度上反映了COPD患者久坐不动的本质，还是由COPD病理生理学的各个方面及其最常见的直接原因——长期吸烟所引发，存在大量争论。与后一种观点一致，最近的证据表明，COPD患者加剧的衰老性肌肉流失可能始于数十年吸烟对神经肌肉接头造成的压力，这使患者易于出现肌肉再支配能力过早衰竭，并伴有线粒体功能的各种改变。在此基础上叠加的是COPD病理生理学的各个方面，如高碳酸血症、低氧血症和炎症，这些也可导致肌肉萎缩。本综述将总结关于导致COPD患者加剧的衰老性肌肉影响的机制的现有知识，以慢性肾脏病为例考虑合并症的潜在作用，并确定新出现的肌肉损伤分子机制，包括线粒体通透性转换作为肌肉萎缩的一种机制，以及芳烃受体的慢性激活在推动COPD肌肉病理生理学中的作用。
